Entecavir for Treatment of Lamivudine-Refractory, HBeAg-Positive Chronic Hepatitis B

Morris Sherman, Cihan Yurdaydin, Jose Sollano, Marcelo Silva, Yun Fan Liaw, Janusz Cianciara, Anna Boron-Kaczmarska, Paul Martin, Zachary Goodman, Richard Colonno, Anne Cross, Gail Denisky, Bruce Kreter, Robert Hindes

Research output: Contribution to journalArticle

363 Scopus citations

Abstract

Background & Aims: Lamivudine treatment is associated with frequent development of resistant hepatitis B virus (HBV) and loss of treatment benefit. In preclinical and phase II studies, entecavir demonstrated potent antiviral activity against lamivudine-resistant HBV. Methods: In this phase III, double-blind trial, hepatitis B e antigen-positive patients who were refractory to lamivudine therapy (persistent viremia or documented YMDD mutations while receiving lamivudine) were randomized to switch to entecavir 1 mg daily (n = 141) or continue lamivudine 100 mg daily (n = 145) for a minimum of 52 weeks. Two coprimary end points were assessed at 48 weeks: histologic improvement and a composite end point (HBV branched DNA <0.7 MEq/mL and alanine aminotransferase [ALT] <1.25 times the upper limit of normal). Results: Histologic improvement occurred in 55% (68/124) of entecavir-treated vs 28% (32/116) of lamivudine-treated patients (P < .0001). More patients on entecavir than lamivudine achieved the composite end point: 55% (77/141) vs 4% (6/145), respectively (P < .0001). Mean change from baseline in HBV DNA was -5.11 log10 copies/mL for entecavir-treated patients and -0.48 log10 copies/mL for lamivudine-treated patients (P < .0001). Virologic rebound because of entecavir resistance substitutions occurred in 2 of 141 of entecavir-treated patients, and genotypic evidence of resistance was detected in 10 patients. The safety profile of entecavir was comparable to lamivudine with fewer ALT flares on treatment. Conclusions: In patients with lamivudine-refractory chronic hepatitis B, switching to entecavir provides superior histologic improvement, viral load reduction, and ALT normalization compared with continuing lamivudine, with a comparable adverse event profile.

Original languageEnglish (US)
Pages (from-to)2039-2049
Number of pages11
JournalGastroenterology
Volume130
Issue number7
DOIs
StatePublished - Jul 2006
Externally publishedYes

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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    Sherman, M., Yurdaydin, C., Sollano, J., Silva, M., Liaw, Y. F., Cianciara, J., Boron-Kaczmarska, A., Martin, P., Goodman, Z., Colonno, R., Cross, A., Denisky, G., Kreter, B., & Hindes, R. (2006). Entecavir for Treatment of Lamivudine-Refractory, HBeAg-Positive Chronic Hepatitis B. Gastroenterology, 130(7), 2039-2049. https://doi.org/10.1053/j.gastro.2006.04.007